The Critical Function of a Peripheral-induced Skin-resident Treg cells in Allergen-Specific Immunotherapy for Atopic Dermatitis 9177

Abstract Description Skin-resident regulatory T (Treg) cells play a critical role in allergen-specific immunotherapy (SIT) for atopic dermatitis (AD), yet their function and origin remain incompletely understood. This study investigated the role of Treg cell lineage involved in SIT for AD patients and mouse models sensitized to house dust mites (HDM). Whole-transcriptome analysis of peripheral blood mononuclear cells (PBMCs) derived from CD4+CD25hiCD127Low cells in SIT responders (R) and non-responders (Non-R) revealed distinct gene expression profiles. In SIT-responsive AD patients, Treg cells exhibited increased expression of retinoic acid-related orphan receptor γt (RORγt). Functional studies using multiple Treg-specific transgenic mouse models undergoing SIT demonstrated that RORγt+FoxP3+ Treg cells are a key protective lineage in the skin, suppressing Th1, Th2, and Th17 cells through IL-10 secretion. Importantly, SIT-induced RORγt+ Treg cells were shown to originate from peripheral tissues rather than the thymus. Two-photon microscopy and parabiosis experiments further revealed that skin-resident RORγt+ Treg cells actively contribute to the SIT-induced immune response by regulating local inflammation and promoting immune tolerance. In conclusion, this study highlights the pivotal role of peripherally-induced, skin-resident RORγt+FoxP3+ Treg cells in mediating the efficacy of SIT, providing valuable insights for advancing therapeutic strategies in AD. Funding Sources Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant No. HI14C1324 and RS-2023-00265913) National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT; grant No. NRF-2021R1A4A5032185).National Research Foundation of Korea, RS-2024-00344273 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)